In 2360, Chief of Starfleet Intelligence AdmiralUhura authorized a covert mission to Romulan space to gather intelligence on the Romulan disease known as the gnawing. (TLEnovel: Catalyst of Sorrows) By 2363, SI was attempting to learn more of the mysterious race known only as the Ferengi but had failed to gather anymoreinformation about this species genetic profile or any other aspect of their civilization. (TLEnovel: The Buried Age)

By the year 2371, SI suspected that there was Borg activity on New Titan. Thus, they dispatched their elite anti-Borg intelligence unit and recruited Captain Jean-Luc Picard as well as Doctor Beverly Crusher to aid the team. Starfleet Intelligence was also responsible for the retrieval operation on Romulus in order to recover Ambassador Spock on Romulus so that he could attend the funeral of Captain James Tiberius Kirk. (TOSnovel: The Return)

Starfleet Intelligence by the year 2387 recommended the Federation keep a close watch on the activities of the Orion Syndicate which led to a crackdown on their operations. Whilst it was initially successful in curbing their threat, the death of their leader Ramius which SI later determined led to the rise of Melani D'ian who controlled 30% of the Syndicate's operations. Analysts determined that her dominance in the Syndicate was the first time in over twenty years that an Orion had taken control of the organization and led some to believe that the race may return as an interstellar power.

In 2406, Admiral Chakotay was promoted to head of the organization, and believed there were at least 30 Undine infiltrators in Starfleet or high-level Federation posts. They did not yet have a foolproof way to detect shapeshifted Undine, but were actively developing such countermeasures. (STwebsite: The Path to 2409)